NCT04505566

INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study

INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy (INSPIRE) Study

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 164 (actual)
• Sponsor: Stephen J. Kim, MD · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The central hypothesis is that inflammation mediators are biomarkers of both systemic diabetes and Diabetic Retinopathy (DR) progression in the aqueous and that sustained topical ketorolac application reduces/suppresses those inflammatory mediators thereby reducing the progression of Diabetic Retinopathy.

Detailed description

Study goals include confirming inflammation mediators are biomarkers of both systemic diabetes and DR progression in the aqueous. Like the vitreous humor, the aqueous reflects localized ocular inflammation, however, is technically easier to collect with less risk. The investigators will also determine the long-term effects of sustained ketorolac application on intraocular cytokine levels, DR progression, and diabetic macular edema (DME) incidence. The proposal is the first to use a cornea-permeable Nonsteroidal anti-inflammatory drug (NSAID) for the treatment of DR. It is believed local inflammation control in the eye will transform future treatment options for diabetic patients facing blindness. Tracking and inhibiting local inflammatory mediators through all DR stages has the capacity to reduce or prevent disability in millions of patients per year. 164 adult type II diabetic mellitus (T2DM) patients, aged 18 years or greater will be enrolled to measure aqueous PGE2 and inflammatory cytokines. Because the pathophysiology of type I disease and the population it effects are different, type I diabetic patients will be excluded. Diabetic retinopathy is broadly categorized as nonproliferative (NPDR) and proliferative (PDR). The international Clinical Disease Severity Scale is a standard classification system consisting of two categories and five stages: the nonproliferative category, stage 1-4 and proliferative category, stage 5. Stage 1 is characterized as "no apparent retinopathy." The nonproliferative stage is further grouped into stage 2 (mild), stage 3 (moderate), and stage 4 (severe). Stage 5 is final stage, PDR. Of the 164 patients enrolled for aqueous PGE2 and inflammatory cytokine measurements, the diabetic participants corresponding to stages 1, 3, and 5 will be classified as patients with no DR (23 patients), with PDR (23 patients), and with moderate NPDR (118 patients). The 118 participants with moderate NPDR will be randomized for Aim 2 described below. In addition, 100 age-matched patients without diabetes who are undergoing unilateral vitrectomy surgery for non-inflammatory conditions such as epiretinal membrane or macular hole will be enrolled as controls. Aim 1 of this project is to measure aqueous PGE2 and inflammatory cytokines during DR progression. Aim 2 of this project is two-fold: 1. Investigate the long-term effects of daily topical application of ketorolac on PGE2 and cytokine levels. 2. Determine how topical application of ketorolac influences DR progression and development of DME.

Conditions

• Diabetic Retinopathy

Interventions

Type	Name	Description
DRUG	Ketorolac 0.45% ophthalmic solution	Ketorolac 0.45% ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.
DRUG	Placebo - Preservative-free artificial tears	Preservative free artificial tears ophthalmic solution 1 drop instilled in both eyes twice daily for 3 years in double-masked fashion.
OTHER	Aqueous PGE2 and inflammatory cytokines measurements	After topical anesthetic, antibiotic and 5% povidone-iodine application, a 30 gauge needle on a 1 ml tuberculin syringe will be inserted into the anterior chamber and used to collect 0.1 ml of aqueous fluid from each eye. Aqueous PGE2 and Inflammatory cytokines will be measured

Timeline

• Start date: 2020-11-09
• Primary completion: 2026-05-01
• Completion: 2026-05-01
• First posted: 2020-08-10
• Last updated: 2026-01-21

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study